Glaucoma surgeons have a full menu of options when it comes to reaching a target IOP. Traditionally, IOP is lowered by various approaches to increase outflow: transconjunctival, trabecular and suprachoroidal. Trabeculectomy and tube shunt surgery, mainstays of outflow surgery, are fraught with rare but potentially grievous complications and high rates of failure.

Now, in addition to trabeculectomies and aqueous tube shunts, multiple minimally invasive techniques improve outflow and have favorable risk profiles, but these methods cannot always effectively lower IOP.

Here, we present the current options that instead focus on reducing aqueous humor production: so-called “inflow procedures.”

TRANS-SCLERAL CYCLOPHOTOCOAGULATION (TCP)

After patients experience medical and surgical failure, surgeons traditionally turn to TCP as a last-ditch effort to reduce IOP. Trans-scleral application with a G probe adjacent to the limbus allows fiberoptic delivery of 810-nm diode laser energy through the sclera 1.2 mm posterior to the surgical limbus, overlying the ciliary body. The 810-nm wavelength laser energy traverses the sclera and is absorbed by melanin pigment in the ciliary epithelium. Treatment consists of about 20 to 24 applications of the laser, 360° for 2000 ms at approximately 2000 mWatts power. Often, a popping sound may be heard when a ciliary process explodes within the eye. Hence, at a histopathologic level, the diode laser causes coagulative necrosis of the ciliary epithelium and stroma.

Application of a diode laser to the ciliary body is effective at lowering IOP, but is accompanied by certain complications. The Diode Laser Ciliary Body Ablation study group defined success as a 20% reduction in IOP and IOP less than 22 mm Hg. The study reported up to 72% success at one year and 52% at year two. However, it also had a high risk of complications: 30% loss of vision, 4% hypotony, and 33% conjunctival burns.¹ Chronic inflammation, phthisis and even sympathetic ophthalmia have been reported with the various iterations of this procedure, and the potential for profound complications has relegated TCP to eyes with end-stage glaucoma and poor visual potential.

To improve this safety profile, the latest generation of procedures directed at reducing aqueous inflow are target-specific cyclophotocoagulative procedures with more favorable side effect profiles: endoscopic cyclophotocoagulation (ECP) and MicroPulse CPC.

ENDOSCOPIC CYCLOPHOTOCOAGULATION

The major advancement of ECP over TCP is its precise placement of thermal laser energy directly on the ciliary processes, thereby reducing collateral damage and enhancing the safety profile. This allows expanded indications earlier in the treatment paradigm, including eyes with good visual potential.

ECP is performed with a microendoscope for video imaging, combined with a 810-nm diode laser, and focused visually by a 670-nm laser aiming beam — all fiberoptically housed within one 20-gauge probe. ECP can be safely performed in pseudophakic/aphakic eyes and in combination with cataract surgery. The most common approach is through a limbal or clear corneal incision of at least 2 mm. A cohesive viscoelastic is injected into the ciliary sulcus to maintain space and improve the view. The laser endoscope is inserted into the incision and advanced between the iris and the anterior lens capsule.

Laser settings range between 200 and 500 mWatts on continuous wave. The desired effect for applying the laser is the whitening and shrinkage of the ciliary tissue. Take care to avoid overtreatment, or explosion, of the ciliary process, which can result in excessive postoperative inflammation. Apply treatment 270° to 360° of the ciliary ring. After removing the endoscope, perform thorough irrigation and aspiration to remove viscoelastic and reduce the risk of a postoperative IOP spike. When there is an anterior chamber lens or insufficient view, use a pars plana approach with a preceding complete vitrectomy.

Histopathologic comparison of ECP and TCP shows that ECP leaves the ciliary stroma intact, preserves ciliary process architecture and ensures the ciliary epithelium remains continuous but with loss of pigment.² In a study of rabbit eyes, TCP caused coagulative necrosis of ciliary tissue with cyclitic membrane formation, while ECP-treated rabbits had disruption of ciliary architecture with a relatively normal process, patent vessels and no cyclitic membrane formation.²

Other ECP procedures include:

• ECP and phacoemulsification. ECP effectively reduces IOP when combined with phacoemulsification more than phacoemulsification alone.³ In a prospective, nonrandomized, matched-control study performed with two years of follow-up, the mean IOP was 1.3 mm Hg lower after two years in the combined ECP group than with phacoemulsification alone. Also, the mean number of medications with ECP plus phaco was 0.4 ± 0.7; phaco alone required 2.0 ± 1.0 medications. There were no serious complications in the study group.
• ECP and plateau iris. In the setting of severe plateau iris, various procedures have been used to try to open the iridocorneal angle, including laser peripheral iridotomy, laser iridoplasty and phacoemulsification. However, none of these procedures addresses the anatomical source of plateau iris — the large and anteriorly rotated ciliary processes. Endoscopic cycloplasty (ECPL) of the ciliary processes causes shrinkage and posterior migration of the ciliary complex. Our prospective study that compared quadrants treated by ECPL vs. baseline and vs. untreated quadrants in the same eye explored this novel procedure for plateau iris.⁴ Along with cataract surgery, ECPL was performed in three quadrants (Figure 1). Anterior chamber depth, angle opening distance and iridocorneal angle increased in the treated quadrants compared to the baseline and untreated quadrant. Parameters associated with ciliary process size and contact with the iris all decreased in treated quadrants compared to baseline and untreated quadrants.
• ECP after aqueous tube shunt. Ciliary body ablation can be helpful as an adjunct in patients who have undergone outflow procedures. We examined such a cohort with prior glaucoma aqueous tube shunts undergoing ECP.⁵ In patients who had a functional Baerveldt glaucoma implant 350 (Abbott Medical Optics) and IOP ≥ 18 mm Hg or in patients with IOP < 18 mm Hg but on oral carbonic anhydrase inhibitors or intolerant to one or more medications, ECP effectively lowered IOP and reduced medications. Mean IOP reduction was greatest at one month (46.1%) and trended down at one-year (31.1%) and two-year (23.3%) data points. Medication reductions were 1.16, 1.72, and 1.45, respectively. No serious complications occurred.
• ECP plus. As stated above, ECP is usually performed from an anterior approach through a corneal incision. However, this only allows access to the anterior portion of the ciliary processes. A pars plana approach allows complete treatment of the ciliary processes; with ECP plus, the pars plana is treated as well (Figure 2). In one study, ECP plus was performed in patients with multiple failed glaucoma filtration surgeries, and IOP higher than 21 mm Hg on maximal tolerated medical therapy.⁶ At one year, patients had a mean IOP reduction of 76.9%. The mean number of glaucoma medications was reduced from 1.1 to 0.7. Enhanced efficacy in the case of ECP plus is associated with a more serious complication profile. Hypotony (5.7%), choroidal detachment (7.5%), CME (7.5%), persistent inflammation (3.8%) and hyphema (3.8%) were seen in the postoperative period.

In summary, ECP can be employed at various places in the treatment of glaucoma. It can be used in advanced stages of glaucoma after one or more filtering procedures have failed. At the time of cataract surgery, ECP can provide additional IOP lowering and reduced dependence on medications in mild to moderate glaucoma patients. ECP combined with outflow procedures (including MIGS procedures) can synergistically lower IOP by reducing aqueous production. In the case of plateau iris, ECPL can treat the anatomical basis for the condition and reverse refractory angle closure. From a pars plana approach, ECP plus can provide additional IOP reduction in advanced glaucoma, but complications are more frequent.

MICROPULSE CYCLOPHOTOCOAGULATION

MicroPulse P3 Cyclophotocoagulation (Cyclo G6, Iridex Corp) offers a novel trans-scleral approach. The same 810-nm diode laser is used, but the continuous wave laser is broken up into a package of repetitive short pulses. The laser has a duty cycle of 31.3% and 0.5 ms bursts coupled with 1.1 ms rest. The MicroPulse P3 (MP3) probe is oriented perpendicular to the globe and placed at the surgical limbus. A notch on the MP3 probe is placed on the globe facing the limbus and rotated throughout the procedure to maintain this radial orientation as the probe sweeps across the treatment zone (Figure 3). Treatment is given for about 90 seconds per hemisphere (total 180 sec) between 9:30 and 2:30 and then 3:30 and 8:30, sparing the temporal and nasal poles.

Multiple groups have reported data on the effectiveness of this approach in lowering IOP. One retrospective study of 19 patients by Kuchar et al defined success as a 20% reduction in IOP and IOP between 6 and 21 mm Hg. Their results showed a 73.7% success rate after initial treatment (n=14) and 89.5% after three patients received a second treatment. This represented a 40.1% mean IOP reduction at last recorded follow up with a mean follow-up of 60 days.⁷ Radcliffe also presented in a meeting abstract a retrospective review of 48 eyes that reported similar results. Results showed a mean IOP reduction of 29.8% and a mean reduction of hypotensive medications of 29.8% with no reported cases of hypotony, macular edema, or phthisis bulbi. Visual decline occurred in one patient due to worsening of pre-existing cataract.⁸ Chew from the National Health University of Singapore presented a meeting abstract of extended follow-up of 14 patients previously enrolled in a prospective trial. The mean pretreatment IOP was 43.3 mm Hg and, after a mean follow-up of 6.5 years, was 24.8 mm Hg, representing a mean IOP reduction of 44.6%. The major caveat behind these data is that patients required four treatments on average to achieve the reported IOPs.⁹

Noecker et al presented in a meeting abstract histopathologic data that show much better tissue preservation with MicroPulse compared to the diffuse coagulative necrosis produced by traditional TCP.¹⁰ Additionally, Lin presented in a meeting abstract ultrasound biomicroscopy before and after the treatment that revealed no evidence of tissue disruption or morphological changes (shrinkage of ciliary processes).¹¹ Interestingly, one hypothesis suggests that the mechanism of action of MicroPulse laser IOP reduction may involve uveoscleral outflow as well as reduction of aqueous humor production. Primates studied after trans-scleral application of Nd-YAG showed an accumulation of aqueous tracers in the suprachoroidal space [Data on file, Iridex Corp].

Additional data on the long-term success here remains withstanding, but the early returns are encouraging. MicroPulse CPC offers a versatile option for surgeons to use at many junctures in the glaucoma treatment algorithm. Reports show that the procedure is fairly benign with regards to complications, therefore it can be used early in therapy and in eyes with good visual potential. Additionally, in patients with uncontrolled pressures, medication intolerance or poor compliance, MicroPulse CPC can provide a low risk, incisionless, sutureless, effective option for swift and sustained IOP reduction.

CONCLUSION

We now have three approaches to ciliary body ablation. TCP is effective at lowering IOP but has the greatest potential for complications due to inflammation and hypotony. Thus, it is generally reserved for more advanced cases. ECP uses a more directed approach with internal application of laser energy directly to the ciliary processes via an endoscopic probe. Compared to TCP, it has fewer side effects related to inflammation and hypotony and can be used in mild glaucoma with phacoemulsification, special cases, such as severe plateau iris, or in more advanced cases, such as those with failed filtration surgery. MicroPulse CPC, the newest iteration of a trans-scleral technique, uses a fraction of the laser energy compared to TCP and, therefore is associated with less inflammation and related side effects. This expands the indications to include those eyes with more moderate disease and good visual potential.

Glaucoma surgeons can now add these several aqueous-reduction procedures to the growing options for the surgical treatment of glaucoma and customization of care. OM

REFERENCES

1. Kosoko O, Gaasterland DE, Pollack IP, Enger CL. Long-term outcome of initial ciliary ablation with contact diode laser transscleral cyclophotocoagulation for severe glaucoma. The Diode Laser Ciliary Body Ablation Study Group. Ophthamology. 1996;103:1294-1302.
2. Pantcheva MB, Kahook MY, Schuman JS, Noecker RJ. Comparison of acute structural and histopathological changes in human autopsy eyes after endoscopic cyclophotocoagulation and trans-scleral cyclophotocoagulation. Br J Ophthalmol. 2007;91:248-252.
3. Francis BA, Berke SJ, Dustin L, Noeker R. Endoscopic cyclophotocoagulation combined with phacoemulsification compared to phacoemulsification alone in medically controlled glaucoma. J Cataract Refract Surg. 2014;40:1313-1321.
4. Francis BA, Pouw A, Jenkins D, et al. Endoscopic Cycloplasty (ECPL) and Lens Extraction in the Treatment of Severe Plateau Iris Syndrome. J Glaucoma. 2016;25:128-133.
5. Francis BA, Kawji AS, Vo NT, Dustin L, Chopra V. Endoscopic cyclophotocoagulation (ECP) in the management of uncontrolled glaucoma with prior aqueous tube shunt. J Glaucoma. 2011; 20;523-527.
6. Tan JC, Francis BA, Noecker R, et al. Endoscopic Cyclophotocoagulation and Pars Plana Ablation (ECP-plus) to Treat Refractory Glaucoma. J Glaucoma. 2016;25;117-122.
7. Kuchar S, Moster M, Reamer CB, Waisbourd M. Treatment outcomes of micropulse transscleral cyclophotocoagulation in advanced glaucoma. Lasers Med Sci. 2016;31:393-396.
8. Radcliffe N, Vold S, Kammer J, et al. MicroPulse Trans-scleral Cyclophotocoagulation (mTSCPC) for the Treatment of Glaucoma Using the MicroPulse P3 Device. American Glaucoma Society abstract. San Diego February 26 - March 1, 2015.
9. Chew P, Aquino M. Long Term Efficacy of MicroPulse Diode Transscleral Cyclophotocoagulation in the Treatment of Refractory Glaucoma. European Glaucoma Society abstract. Prague, Czech Republic, June 19-22, 2016.
10. Maslin J, Chen P, Sinard J, Noecker R. Comparison of Acute Histopathological Changes in Human Cadaver Eyes After MicroPulse and Continuous Wave Trans-Scleral Cyclophotocoagulation. American Glaucoma Society abstract. Fort Lauderdale, FL, March, 2016.
11. Lin SC, Masis M, Babic K. Micropulse Transscleral Diode Laser Cyclophotocoagulation: Short-Term Results and Anatomical Effects. American Glaucoma Society abstract. Fort Lauderdale, FL, March, 2016.

About the Authors

Brett McKnight, MD, is a Glaucoma Fellow at Doheny Eye Institute, Stein Eye Institute David Geffen School of Medicine at UCLA.

Brian A. Francis, MD, MS, is the holder of the Rupert and Gertrude Stieger Endowed Chair at the Doheny Eye Institute. He is a Health Sciences professor of Ophthalmology at the David Geffen School of Medicine, UCLA. He is also the director of Glaucoma Services and Glaucoma Fellowship director at the Doheny Eye Institute. His research interests include novel glaucoma surgical techniques and glaucoma diagnostic technologies. Dr. Francis is a consultant for Beaver-Visitec International.